The main objective of the proposed research is to investigate the relative capacities of hepatic and extrahepatic tissues to metabolize a number of drug substrates during pre- and post-natal development and the effects of environmental factors (e.g. nutrition, heavy metals and disease) upon these capabilities. Characterization of the monoxygenase system will include the measurement of electron transfer components such as cytochrome P-450 and cytochrome b5 and pathways of drug metabolism including oxidation, reduction, hydrolysis and conjugation using multiple drug substrates. Determination of the acute and chronic effects of environmental and disease factors, hormones and drug substances will be investigated in order to understand the biochemical mechanisms of toxicity and teratogenesis. The characterization of drug metabolism during development and its alteration by the environment will aid in the delineation of the biochemical mechanisms of regulation of enzymic activities. The information derived from these basic biochemical studies will help to develop rational, safe and effective use of therapeutic drugs in sick infants, children and pregnant women and will lead to an understanding and hence prevention of birth defects.